pseudomonas aeruginosa nosocomial pneumonia 1191
has not previously been performed. Pneumonia classification of P. aeruginosa may have important clinical implications, especially from treatment and infection control perspectives where typically ventilator-associated pneumonia (VAP) is primarily evaluated. Therefore, we set out to perform an ana- lysis of a multinational study of Pa-NP with the following objectives: first, to describe and compare the mortality asso- ciated with Pa-NP according to pneumonia classification; second, to identify and compare risk factors for hospital mortality and IIAT according to pneumonia classification.
methods Study Design and Ethical Standards
We conducted a retrospective cohort study in 12 hospitals in 5 countries (United States, 3; France, 2; Germany, 2; Italy, 2; and Spain, 3). Eligible consecutive patients were aged 18 years or older and admitted for their index hospitalization within 36 months prior to study initiation in 2013. All eligible patients met a clinical diagnosis of NP defined as new or progressive infiltrates consistent with pneumonia on chest radiograph or computed tomography and either a temperature higher than 38.3°C or leukocytosis greater than 10,000 cells/mm3 or both. To be eligible patients had to have P. aeruginosa cultured from blood or a respiratory specimen collected from the following: sputum, pleural fluid, flexible bronchoscopy with protected specimen brush, bronchoalveolar, or transbronchial biopsy, “mini-bronchoalveolar” sample, and tracheobronchial aspi- rate in intubated patients. Microbiologic cultures had to be obtained within the 24-hour period surrounding initiation of antibiotics. Pa-NP was classified as COP, HAP, and VAP according to the location and conditions of the onset of infection (COP: prior to hospital admission; HAP: developing during the hospital stay; VAP: developing while receiving mechanical ventilation). Patients with COP had to have 1 or more of the following characteristics to be included: hospita- lized in an acute care hospital for 2 or more days within 90 days of infection; resided in a nursing home or long-term care facility; received recent intravenous antibiotic therapy, che- motherapy, or wound care in the past 30 days; or attended a hospital or hemodialysis clinic. Each investigator obtained approval from an independent ethics committee or institu- tional review board at his or her institution.
End Points and Covariates
The primary end point examined was hospital mortality. We also examined other important covariates to include demo- graphic characteristics,MDR status of the P. aeruginosa isolate, and comorbidities (acute coronary syndrome, valvular heart disease, hypertension, venous thromboembolism, chronic obstructive pulmonary disease, asthma, other chronic respiratory diseases, and diabetes mellitus). Patients were also classified according to whether they received IIAT.
Definitions
To be classified as MDR, the P. aeruginosa isolate had to be nonsusceptible to at least 1 agent in at least 3 of the following antimicrobial categories: aminoglycosides, antipseudomonal carbapenems, antipseudomonal cephalosporins, anti- pseudomonal fluoroquinolones, antipseudomonal penicillins plus β-lactamase inhibitors, monobactams, phosphonic acids, and polymixins.16 Antimicrobial treatment was deemed to represent IIAT if the initially prescribed antibiotic regimen was not active against the identified isolate on the basis of in vitro susceptibility testing or was administered more than 24 hours following respiratory specimen collection.17 Microbiology laboratories determined antimicrobial susceptibility of the isolates using disk diffusion or automated testing methods according to established guidelines and breakpoints.18,19
Statistical Analyses
Continuous variables were reported as means with standard deviations. Differences between mean values were tested via the t test. Categorical data were summarized as proportions, and the χ2 test or Fisher exact test for small samples was used to examine differences between groups. We developed several multiple logistic regression models to identify clinical risk fac- tors associated with hospital mortality and IIAT. Risk factors that were significant at P≤.20 in the univariate analyses, as well as all biologically plausible factors even if they did not reach this level of significance, were included in the corresponding mul- tivariable analyses. All variables entered into the models were examined to assess for collinearity, and interaction terms were tested. The most parsimonious models for the predictors of hospital mortality and IIAT respectively were computed and their fit was tested with the area under the receiver operating curve and the Hosmer-Lemeshow goodness-of-fit test. All tests were 2-tailed, and a P value<.05 was deemed a priori to represent statistical significance. On the basis of our prior experience and available publications, we estimated that the hospital mortality for COP would be approximately 20% and the hospitalmortality forHAP and VAPwould be between 35% and 40%. Using a 2-sided estimate with a P value of .05 and 80%power required at least 138 patients per pneumonia type to yield statistically meaningful estimates. Thus our goal prior to performing the study was to have at least 150 patients per pneumonia type during study recruitment and data collection to ensure that ourmortality analysis would be valid. All analyses were performed with SPSS software, version 19.0 (IBM).
results
Seven hundred forty-two patients with Pa-NP met the inclu- sion criteria and were enrolled in the study. There were 258 patients (34.8%) from the United States, 141 (19.0%) from France, 120 (16.2%) from Germany, 115 (15.5%) from Spain, and 108 (14.6%) from Italy. A diagnosis of pneumonia was
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